..The hypothesis is that the suppression of this pathway results in sensitization to anti-HER2 agents. However, this combinatorial strategy has not been comprehensively tested in models of trastuzumab and lapatinib resistance...

..Our data show that deregulation of the PI3K pathway, either through loss-of-function mutations in PTEN or dominant activating mutations in PIK3CA, leads to lapatinib resistance, which can be effectively reversed by NVP-BEZ235...

..Pharmacodynamic analyses in mitotic cells of both skin and tumor provided proof of mechanism for Aurora A kinase inhibition. A more potent, selective, second-generation Aurora A kinase inhibitor, MLN8237, is in clinical development...

..A phase I study was performed in patients with advanced solid tumors to determine the maximum tolerated dose (MTD), establish a safety profile, and to evaluate pharmacokinetics and efficacy of the drug...

..Thus, the overall management of breast cancer will increasingly require an understanding of breast cancer heterogeneicity, the biological nature of any given tumor as well the existence of increased personalized treatment options...

..Overall, results from clinical trials are sufficiently compelling to consider 1 year of adjuvant trastuzumab treatment for women with HER-2-positive EBC based on the risk:benefit ratio demonstrated in these studies...

..Thus, the rationale for EGFR-targeted approaches to cancer treatment is apparent and now well established, and there is increasing evidence that they may represent a significant contribution to cancer therapy...

Unconventional secretion is a major contributor of cancer cell line secretomes

..The unconventional secretion of proteins into the extracellular space exposes a new layer of genome post-translational regulation and reveals an untapped source of potential tumor biomarkers and drug targets...

Molecular prescreening to select patient population in early clinical trials

..We think that our findings will allow designing and executing better comparative proteomics projects and will help to avoid reaching false conclusions in the field of proteomics biomarker discovery...

..PBMC were stimulated ex vivo to determine the individual biological variability of an ex vivo assay measuring pSMAD expression. This assay performed sufficiently well to allow its future use in a clinical trial of a TGF-beta inhibitor...

Phase I pharmacokinetic and pharmacodynamic study of weekly 1-hour and 24-hour infusion BMS-214662, a farnesyltransferase inhibitor, in patients with advanced solid tumors